Patients with multiple system atrophy (MSA), a sporadic and progressive neurodegenerative disorder, suffer from orthostatic hypotension, postprandial hypotension and supine hypertension. Hypotension causes presyncopal symptoms usually within seconds of standing and requires the patient to sit or lie down to prevent syncope. Supine hypertension reduces sleep quality through excessive nocturnal diuresis, and results in blood volume loss during the night, which aggravates orthostatic hypotension during the day. New strategies of treatments are required which take into account this cycling between hypertension and hypotension. Recent studies in our laboratory have yielded the unexpected observation that sympathetic activity is present in MSA, but is not subject to normal control mechanisms. This sympathetic activity produces inappropriate supine hypertension, but is not able to prevent the profound orthostatic hypotension. The identification of residual sympathetic activity in MSA has important implications for new therapeutic approaches. We hypothesize that a bionic baroreflex system based on electrical epidural spinal stimulation will help to replace the missing control of sympathetic activity by the vasomotor center. Preliminary data in animals showed that such a system maintained blood pressure during orthostatic stress. The purpose of this grant proposal is to search for an effective and practical bionic baroreflex system for patients with MSA and baroreflex failure. First, we will develop a prototype bionic baroreflex control system using baroreflex-denervated rats. Then, the system will be applied to control artificially, the muscle sympathetic nerve activity in patients who already have an epidural electrical stimulator in place for the control of chronic pain. A Phase II study would involve studies in animals and in patients with MSA to determine the long-term efficacy of the bionic baroreflex system in improving blood pressure control.